Semen from 13 bulls, eight with clinical bovine spongiform encephalopathy (BsE), was used to artificially inseminate (AI) 167 cows with clinical BSE, and their resultant embryos were collected non‐surgically seven days after Al. The viable and non‐viable embryos with intact zonae pellucidae were washed 10 times (as recommended by the International Embryo Transfer Society) then frozen. Later, 587 of the viable embryos were transferred singly into 347 recipient heifers imported from New Zealand, and 266 live offspring were born of which 54.1 per cent had a BSE‐positive sire and a BSE‐positive dam. The recipients were monitored for clinical signs of BSE for seven years after the transfer, and the offspring were monitored for seven years after birth. Twenty‐seven of the recipients and 20 offspring died while being monitored but none showed signs of BSE. Their brains, and the brains of the recipients and offspring killed after seven years, were examined for BSE by histopathology, PrP immunohistochemistry, and by electron microscopy for scrapieassociated fibrils. They were all negative. In addition, 1020 non‐viable embryos were sonicated and injected intracerebrally into susceptible mice (20 embryos per mouse) which were monitored for up to 700 days, after which their brains were examined for spongiform lesions. They were all negative. It is concluded that embryos are unlikely to carry BSE infectivity even if they have been collected at the end‐stage of the disease, when the risk of maternal transmission is believed to be highest.

Bovine spongiform encephalopathy (BSE) and its human equivalent, variant Creutzfeldt–Jakob disease (vCJD), are caused by the same strain of infectious agent, which is similar to, but distinct from, >20 strains of their sheep scrapie homologue. A better understanding of the molecular strain determinants could be obtained from cells in monoculture than from whole animal studies where different cell targeting is commonly a strain‐related feature. Although a few cell types can be infected with different strains, the phenotypes of the emergent strains have not been studied. We have cured the scrapie‐infected, clonal SMB cell line with pentosan sulfate, stably re‐infected it with a different strain of scrapie and shown that biological properties and prion protein profiles characteristic of each original strain are propagated faithfully in this single non‐neuronal cell type. These findings attest to the fact that scrapie strain determinants are stable and host‐independent in isolated cells.

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or ‘prion’ diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains 1 , 2 , 3 , 4 . We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species 5 , 6 , 7 . This BSE ‘signature’ has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant 6 , 8 , providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt–Jakob disease (CJD), referred to as ‘new variant’ CJD (vCJD) 9 , have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France 10 . This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

ers 1991, Gunnarsson and Franklin 1992). In Hungary, lincomycin was the second potent antibiotic which gained nationwide use for the treatment of swine dysentery from the end of the 1970s. The proportion of strains resistant to lincomycin increased gradually until the middle of the 1980s. The proportions of resistant strains isolated in the periods 1983 to 1987 and 1988 to 1992 were not markedly different. Nearly half the strains are sensitive even today. This result is in contrast with data obtained by other authors (Messier and others 1990, Ronne and Szancer 1990, Walter and Kinyon 1990, Smith and others 1991). An explanation for the small number of lincomycin-resistant strains in Hungary may be that since the beginning of the 1980s tiamulin has been used widely while lincomycin has been used less frequently. At present tiamulin is considered to be the most effective antibiotic (Messier and others 1990, Walter and Kinyon 1990, Ronne and Szancer 1991, Messier 1992, Gunnarsson and Franklin 1992), and resistance to it has been observed only very rarely (Messier 1992). These results are in agreement with the present findings; however, resistance to tiamulin is likely to develop. Few data are available on the effect of monensin on S hyodysenteriae (Molnar and others 1987, Kyriakis 1989). Molnar and others (1987) found monensin to be only moderately effective for the treatment of swine dysentery but satisfactory for its prevention. These observations were also supported by results obtained in the field, although on farms where monensin had been used for

Veterinary RecordVolume 138, Issue 22 p. 546-548 Short Communication Detection of BSE infectivity in brain and spleen of experimentally infected sheep J. D. Foster, J. D. Foster Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorM. Bruce, M. Bruce Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorI. McConnell, I. McConnell Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorA. Chree, A. Chree Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorH. Fraser, H. Fraser Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this author J. D. Foster, J. D. Foster Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorM. Bruce, M. Bruce Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorI. McConnell, I. McConnell Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorA. Chree, A. Chree Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this authorH. Fraser, H. Fraser Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Ogston Building, Edinburgh, EH9 3JFSearch for more papers by this author First published: 01 June 1996 https://doi.org/10.1136/vr.138.22.546Citations: 20Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume138, Issue22June 1996Pages 546-548 RelatedInformation

Amyotrophic lateral sclerosis (ALS) resembles the spongiform encephalopathies in its dual pattern of inherited and sporadic cases, its uniform prevalence in different populations, its late onset (suggestive of a long incubation period) and its pathological picture of neuronal degeneration without inflammation. There is a well‐established protocol for primary transmission of scrapie and related diseases to mice. Using this, we inoculated four long‐lived, inbred, mouse strains with cord material fresh‐frozen within three hours of death, from a case of ALS or a control case. No motor neuron loss, gliosis or tract demyelination was found in the experimental group. Fifty per cent of each group were observed for more than 600 days. Two types of lesions were found in these animals at death: widespread foci of white matter vacuolation and bilateral thalamic mineral deposits. They were present in the control group at the same incidence and severity as in the experimental group and were thus considered to represent an age‐related change. Attention is drawn to them because they have been claimed as significant when found in a transgenic model of spongiform encephalopathy. The results of our carefully‐controlled experiment suggest that it is unlikely that ALS is caused by a scrapie‐like agent capable of transmission to mice.

Transmissions of bovine spongiform encephalopathy (BSE) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. Transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with BSE have given similar results to direct BSE transmissions from cattle. Therefore the BSE agent has retained its identity when passaged through a range of species and the 'donor' species has little specific influence on disease characteristics in mice, adding to evidence for an agent-specific informational molecule. On transmission of BSE or scrapie to mice the incubation periods are long compared with subsequent mouse-to-mouse passages (the 'species barrier'). Contributing factors include a low efficiency of infection on interspecies transmission, the apparent failure of intracerebrally injected 'foreign' inoculum to establish infection directly in mouse brain and the selection of variant strains of agent which replicate most readily in the new host species.

Transmission from four cases of bovine spongiform encephalopathy (BSE) to mice resulted in neurological disease in 100% of recipient animals, after incubation periods of between 265 and 700 days post-injection. The results from the four cases were very similar to one another. There were major differences in the incubation period between the four inbred strains of mice tested, and even between strains of the same Sinc genotype, and the incubation periods of Sinc heterozygote mice were much longer than those for any of the inbred strains. Transmission from a case of natural scrapie differed in two important respects: there were no differences in the incubation period between mouse strains of the same Sinc genotype, and that of the heterozygotes was between those of the Sinc homozygotic parental strains. The distribution of vacuolar degeneration in the brains of mice infected with scrapie also differed from those infected with the BSE isolates. Transmission was also achieved from formol-fixed BSE brain. These results show that the same strain of agent caused disease in the BSE cases, and that the relationship of BSE to scrapie in sheep is unclear.